e13541 Oxysterols are oxygenated derivatives of cholesterol. They have nuclear receptors and have been shown to pass cell membranes and the blood-brain barrier at a faster rate than cholesterol itself. In addition, oxysterols have been ascribed a number of important roles in connection with cholesterol turnover, atherosclerosis, apoptosis, and necrosis. Oxysterols have been shown to have antitumor effects on experimental models. These compounds however may be toxic and to our knowledge, although some derivatives have been tested in animals, none have reached the clinical level. 24-ethyl-cholestane- 3β,5α,6α-triol is a new oxysterol developed in our lab. An oral form of this compound has been tested in mice and rats and has shown neither acute nor chronic toxicity. It has also been tested on animal tumor models and on human cancer xenografts. The results of these tests were very promising showing an anti-tumor activity on a panel of tumor cell lines. Our experiments on humans have shown no toxicity for this drug. Many patients with a variety of solid tumors all of whom have received many lines of chemotherapy and considered refractory to any conventional therapy have received this new drug. We observed in most of these patients a rapid and dramatic improvement in their quality of life and a fast pain control. Some patients could stop taking high doses of opioids within 1 or 2 days. A high rate of clinical benefit has also been observed in a variety of solid tumors including lung, breast, pancreatic, ovarian and uterine cancers, associated in some cases with a sharp decrease in tumor markers. Some patients with brain tumors (glioblastomas) have also responded to this therapy. No significant financial relationships to disclose.
e20500 Background: Oxygenated derivatives of cholesterol, oxysterols, have different physicochemical properties acting on cell membranes. Agents belonging to this class of compounds have been found to induce apoptosis and to harbor antitumor activity demonstrated in vitro and in vivo. 24-ethyl-cholestane- 3β, 5α, and 6α-triol is a new oxysterol developed in our lab. Unlike other derivatives, it is, to our knowledge, the first tested in the clinic. Methods: We have previously reported encouraging and rapid results observed in patients suffering from a variety of solid tumors with an improvement of their quality-of- life and without side- effects. We have treated eight patients suffering from different types of sarcomas on a compassionate basis because we did not have any ongoing trial in sarcomas. Furthermore, most of these patients would not have been eligible for a clinical trial because of their bad performance-status. Three patients were suffering from carcinosarcomas, one from angiosarcoma, one from osteosarcoma, one from chondrosarcoma, one from undifferentiated sarcoma and one from Ewing sarcoma. Most of them were pretreated with chemotherapy and radiotherapy and most of them were in bad clinical conditions. Seven patients were females and one male with ages ranging from 21 to 82 (median age 55y). Results: None of these 8 patients experienced any side-effect despite the fact that one of them was taking a mild chemotherapy in association with oxysterol. This patient was excluded from the evaluation of the response to therapy. Among the 7 patients evaluable for response, we observed 4 complete responses (one of them confirmed by PET scan), two stable diseases and one progressive disease. The complete responses were observed in one osteosarcoma, one Ewing sarcoma, one angiosarcoma and one carcinosarcoma. As with our previous experience with this drug, no clinical or biological side-effect was observed and symptom control was achieved rapidly in all 6 symptomatic patients. Conclusions: We believe that this new compound deserves to be tested in phase II trials in patients suffering from sarcomas.
e20587 Background: Hydroxysterols are oxygenated derivatives of cholesterol. They have been shown to interfere with proliferation and cause the death of many cancer cell types, such as leukaemia, glioblastoma, colon, breast and prostate cancer cells. They control the transcription and the turnover of the key enzyme in cholesterol synthesis. Hydroxysterols interfere with PI3K/AKT, MAPK/ERK, hedgehog and Wnt pathways of proliferation and differentiation. When administered in vitro to cancer cell lines, hydroxysterols invariably both slow down proliferation and provoke cell death. Many of these compounds show antitumor activity in experimental models and most of them are very toxic. (24-ethyl-cholestane- 3β,5α,6α-triol) is the first oxysterol being tested in the clinic. It is also one of the safest in this class of compounds. Methods: We have treated with this new drug 18 patients suffering from Non-small cell lung cancer (NSCLC); sixteen males and two females. Thirteen had adenocarcinomas and five had squamous-cell carcinoma. The median age was 65. Sixteen patients had a stage IV disease and two had a stage III disease. Seven had a PS: 1, seven had a PS: 2 and four had a PS:3. Seventy-five percent were symptomatic and fifty percent were taking pain killers. Six patients only did not receive previous chemotherapy and five received radiotherapy. Patients received daily 10 mg/Kg of oral (24-ethyl-cholestane- 3β,5α,6α-triol) divided in 3 equal doses, until disease progression. Results: Twelve patients had a partial response (PR), three patients had a stable disease (NC) and three patients had a disease progression (PD). The median duration of response was 8 months but 2 patients are still under treatment. No toxicity was observed so ever. Seventy-five percent of symptomatic patients had a remarkable symptom control. Conclusions: These encouraging results make this new and safe drug a good candidate for further clinical trials either alone or in association with other drugs for the treatment of NSCLC.
Background: Recent studies indicate comparable survival after thermal ablation and liver resection for colorectal cancer liver metastases (CRCLM). Awating Results from randomized trials, the aim was to compare survival after microwave ablation (MWA) versus liver resection for CRCLM in a population-based study using propensity score matching. Materials and Methods: All patients undergoing liver resection or MWA as a first intervention for CRCLM measuring less than 3 cm in Sweden between 2013 and 2016 were included from a nationwide registry. Treatment effect was estimated after propensity score (PS) matching, adjusting for patient and tumour factors hypothesised to affect the choice of treatment approach. Survival was illustrated with Kaplan-Meier curves and compared with the log-rank test. Cox regression was used to estimate predictors of survival presented as hazard ratios (HR). Results: The unmatched cohorts (82 patients with MWA, 645 patients with resection) differed significantly regarding age, American Society of Anesthesiologists class, Charlson comorbidity index, primary tumour location, number of metastases and previous chemotherapy. Before matching, 3-and 4-year OS differed significantly favouring resection over MWA (76% and 69%, 67% and 42%, p=0.005). After PS matching (201 resection patients, 70 MWA patients), no difference in OS after 3 and 4 years was shown between both groups (76% and 76%, 68% and 54%, p=0.253). Univariate HR for OS was 1.43 (95% CI 0.772 -2.651, p=0.255) for the matched MWA group compared with the resection group. Conclusion: No significant difference in OS was found in patients undergoing MWA versus resection as a first-line intervention for CRCLM in the PS analysis used to minimize the effect of confounding by indication. This supports the potential role of MWA as a valid first treatment for patients with CRCLM.
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